Identification

Name
Gemcitabine
Accession Number
DB00441
Description

Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide").

Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 263.1981
Monoisotopic: 263.071762265
Chemical Formula
C9H11F2N3O4
Synonyms
  • 2'-Deoxy-2',2'-difluorocytidine
  • 2',2'-Difluorodeoxycytidine
  • 4-amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one
  • Gemcitabin
  • Gemcitabina
  • Gemcitabine
  • Gemcitabinum
External IDs
  • LY-188011
  • LY188011

Pharmacology

Indication

Gemcitabine is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy; metastatic ovarian cancer; inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer; and locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Gemcitabine is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (or DNA synthesis phase of the cell cycle), stopping normal development and division. Gemcitabine blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemcitabine blocks the incorporation of the thymidine nucleotide into the DNA strand. It demonstrates dose-dependent synergistic activity with cisplatin in vitro. In vivo, gemcitabine showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Gemcitabine was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to gemcitabine 4 hours before cisplatin produced the greatest interaction.

Mechanism of action

Gemcitabine inhibits thymidylate synthetase, leading to inhibition of DNA synthesis and cell death. Gemcitabine is a prodrug so activity occurs as a result of intracellular conversion to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate by deoxycitidine kinase. Gemcitabine diphosphate also inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside triphosphates required for DNA synthesis. Finally, Gemcitabine triphosphate (diflurorodeoxycytidine triphosphate) competes with endogenous deoxynucleoside triphosphates for incorporation into DNA.

TargetActionsOrganism
ADNA
cross-linking/alkylation
Humans
ARibonucleoside-diphosphate reductase large subunit
inhibitor
Humans
UThymidylate synthase
inhibitor
Humans
UUMP-CMP kinase
inhibitor
Humans
Absorption

The pharmacokinetics of gemcitabine are described by a 2-compartment model.

Volume of distribution
  • 50 L/m^2 [infusions lasting <70 minutes]
  • 370 L/m^2 [long infusions]
Protein binding

Plasma protein binding is negligible (<10%)

Metabolism

Transformed via nucleoside kinases to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate. Can also undergo deamination via cytidine deaminase to an inactive uracil metabolite (dFdU).

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Route of elimination

Within one (1) week, 92% to 98% of the dose was recovered, almost entirely in the urine. Gemcitabine (<10%) and the inactive uracil metabolite, 2´-deoxy-2´,2´-difluorouridine (dFdU), accounted for 99% of the excreted dose.

Half-life

Gemcitabine half-life for short infusions ranged from 42 to 94 minutes, and the value for long infusions varied from 245 to 638 minutes, depending on age and gender, reflecting a greatly increased volume of distribution with longer infusions.

Clearance
  • 92.2 L/hr/m2 [Men 29 yrs]
  • 75.7 L/hr/m2 [Men 45 yrs]
  • 55.1 L/hr/m2 [Men 65 yrs]
  • 40.7 L/hr/m2 [Men 79 yrs]
  • 69.4 L/hr/m2 [Women 29 yrs]
  • 57 L/hr/m2 [Women 45 yrs]
  • 41.5 L/hr/m2 [Women 65 yrs]
  • 30.7 L/hr/m2 [Women 79 yrs]
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Myelosuppression, paresthesias, and severe rash were the principal toxicities, LD50=500 mg/kg (orally in mice and rats)

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Gemcitabine Metabolism PathwayDrug metabolism
Gemcitabine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Ribonucleoside-diphosphate reductase large subunit---(A;A)A allele, homozygous / A allele, homozygousADR Directly StudiedPatients with this genotype have increased risk of neutropenia and neurotoxicity with gemcitabine.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirGemcitabine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Gemcitabine.
AcarboseAcarbose may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Gemcitabine.
AcetaminophenAcetaminophen may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Gemcitabine which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Gemcitabine which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Product Ingredients
IngredientUNIICASInChI Key
Gemcitabine hydrochlorideU347PV74IL122111-03-9OKKDEIYWILRZIA-OSZBKLCCSA-N
International/Other Brands
Abine (Dosa) / Abingem (Miracalus) / Acytabin (Intas) / Celgem (Alkem) / Celzar (Celon) / Cytogem (Dr Reddys) / Daplax (Dr Reddys) / Dercin (Egis) / Eriogem (Eriochem) / Fotinex (Fada) / Gebina (Aspen) / Gembio (Bioprofarma) / Gemcired (Dr Reddys) / Gemita (Fresenius) / Gezt (Richmond) / Gitrabin (Actavis) / Gramagen (Lilly) / Jemta (Sandoz) / Nallian (Gedeon Richter) / Oncogem (Grey Inversiones) / Ribozar (Ribosepharm) / Tabin (Crinos) / Xtroz (Ranbaxy)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act GemcitabineSolutionIntravenousActavis Pharma Company2016-05-022019-08-13Canada flag
Act GemcitabinePowder, for solutionIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act GemcitabinePowder, for solutionIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
GemcitabineInjection, solution100 mg/1mLIntravenousBluePoint Laboratories2018-05-25Not applicableUS flag
GemcitabineInjection, solution38 mg/1mLIntravenousHospira, Inc.2011-08-22Not applicableUS flag
GemcitabineInjection, solution100 mg/1mLIntravenousAccord Healthcare Inc.2018-01-24Not applicableUS flag
GemcitabineInjection, solution38 mg/1mLIntravenousMylan Laboratories Limited2017-12-31Not applicableUS flag
GemcitabineInjection, solution100 mg/1mLIntravenousBluePoint Laboratories2018-05-25Not applicableUS flag
GemcitabineInjection, solution38 mg/1mLIntravenousHospira, Inc.2011-08-26Not applicableUS flag
GemcitabineInjection, solution100 mg/1mLIntravenousBluePoint Laboratories2018-05-25Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aj-gemcitabinePowder, for solutionIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
Aj-gemcitabinePowder, for solutionIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
Aj-gemcitabinePowder, for solutionIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
GemcitabineInjection, powder, lyophilized, for solution38 mg/1mLIntravenousHospira, Inc.2010-11-15Not applicableUS flag
GemcitabineInjection, solution38 mg/1mLIntravenousApotex Corp.2018-03-202021-01-31US flag
GemcitabineInjection, powder, lyophilized, for solution1 g/25mLIntravenousDr. Reddy's Laboratories Limited2011-07-25Not applicableUS flag
GemcitabineInjection1 g/26.3mLIntravenousArmas Pharmaceuticals Inc.2020-01-15Not applicableUS flag
GemcitabineInjection, powder, lyophilized, for solution200 mg/5mLIntravenousSagent Pharmaceuticals2014-12-29Not applicableUS flag
GemcitabineInjection, solution38 mg/1mLIntravenousIngenus Pharmaceuticals, LLC2019-02-26Not applicableUS flag
GemcitabineInjection38 mg/1mLIntravenousActavis Pharma, Inc.2016-04-122020-09-30US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L01BC05 — Gemcitabine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Pyrimidine 2'-deoxyribonucleosides
Direct Parent
Pyrimidine 2'-deoxyribonucleosides
Alternative Parents
Pyrimidones / Aminopyrimidines and derivatives / Hydropyrimidines / Imidolactams / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Fluorohydrins / Azacyclic compounds / Oxacyclic compounds
show 7 more
Substituents
Alcohol / Alkyl fluoride / Alkyl halide / Amine / Aminopyrimidine / Aromatic heteromonocyclic compound / Azacycle / Fluorohydrin / Halohydrin / Heteroaromatic compound
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, pyrimidine 2'-deoxyribonucleoside (CHEBI:175901)

Chemical Identifiers

UNII
B76N6SBZ8R
CAS number
95058-81-4
InChI Key
SDUQYLNIPVEERB-QPPQHZFASA-N
InChI
InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
IUPAC Name
4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
SMILES
NC1=NC(=O)N(C=C1)[[email protected]@H]1O[[email protected]](CO)[[email protected]@H](O)C1(F)F

References

Synthesis Reference

John A. Weigel, "Process for making gemcitabine hydrochloride." U.S. Patent US6001994, issued May, 1995.

US6001994
General References
  1. Link [Link]
Human Metabolome Database
HMDB0014584
KEGG Drug
D02368
KEGG Compound
C07650
PubChem Compound
60750
PubChem Substance
46506425
ChemSpider
54753
RxNav
12574
ChEBI
175901
ChEMBL
CHEMBL888
ZINC
ZINC000018279854
Therapeutic Targets Database
DAP001246
PharmGKB
PA449748
PDBe Ligand
GEO
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Gemcitabine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
1p62 / 2no0 / 2vpp / 4pd5 / 6nl4
FDA label
Download (105 KB)
MSDS
Download (69.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingOtherMalignant Neoplasm of Pancreas1
4Active Not RecruitingTreatmentAdenocarcinoma of the Pancreas1
4Active Not RecruitingTreatmentAdenocarcinomas / EGFR Positive Non-small Cell Lung Cancer1
4Active Not RecruitingTreatmentLung Squamous Cell Carcinoma / Squamous Non-small-cell Lung Cancer1
4CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)2
4Not Yet RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
4RecruitingTreatmentAdenocarcinoma of the Pancreas / Chemotherapy Effect1
4RecruitingTreatmentNasal and Nasal-type NK/T-cell Lymphoma1
4RecruitingTreatmentPancreatic Ductal Adenocarcinoma1
4RecruitingTreatmentPeripheral T Cell Lymphoma (PTCL) / Peripheral T-Cell Lymphoma (PTCL)1

Pharmacoeconomics

Manufacturers
  • Teva parenteral medicines inc
  • Eli lilly and co
Packagers
  • Eli Lilly & Co.
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous; Parenteral40 MG/ML
SolutionIntravenous1 g
SolutionIntravenous10 mg
Injection, solution, concentrateIntravenous; Parenteral100 MG/ML
Powder, for solutionParenteral38 MG/ML
Powder, for solutionParenteral1 G
Powder, for solutionParenteral2 G
Powder, for solutionParenteral200 MG
Injection, solution, concentrateIntravenous; Parenteral38 MG/ML
Injection, solutionParenteral10 MG/ML
InjectionIntravenous1 g/26.3mL
InjectionIntravenous2 g/52.6mL
InjectionIntravenous200 mg/5.26mL
InjectionIntravenous38 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous1 g/1
Injection, powder, lyophilized, for solutionIntravenous200 mg/1
Injection, powder, lyophilized, for solutionIntravenous40 mg/1mL
Injection, solutionIntravenous1 g/26.3mL
Injection, solutionIntravenous100 mg/1mL
Injection, solutionIntravenous2 g/52.6mL
Injection, solutionIntravenous200 mg/5.26mL
Injection, solutionIntravenous38 mg/1mL
Powder, for solutionIntravenous
PowderIntravenous
Injection, powder, lyophilized, for solutionIntravenous1 g/25mL
Injection, powder, lyophilized, for solutionIntravenous200 mg/5mL
SolutionIntravenous2 g/52.6ml
Injection, powder, lyophilized, for solutionIntravenous2 g/50mL
Injection, powder, lyophilized, for solutionIntravenous38 mg/1mL
SolutionIntravenous
InjectionIntravenous1 g
InjectionIntravenous200 mg
InjectionIntravenous1000 mg
Injection, solution, concentrateIntravenous1000 mg/25ml
InjectionIntravenous2000 mg
Injection, solution, concentrateIntravenous2000 mg/50ml
Injection, solution, concentrateIntravenous200 mg/5ml
Injection, powder, lyophilized, for solutionIntravenous1400 mg
Injection, powder, lyophilized, for solutionIntravenous2000 mg
Injection, solution, concentrateParenteral1000 mg/10ml
Injection, solution, concentrateParenteral200 mg/2ml
Injection, solution, concentrateParenteral2000 mg/20ml
Injection
Injection, powder, lyophilized, for solutionIntravenous1 g
Injection, powder, lyophilized, for solutionIntravenous200 mg
InjectionIntravenous1000 mg/100ml
InjectionIntravenous200 mg/20ml
InjectionIntravenous500 mg/50ml
Injection, solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous1000 mg
Injection, powder, lyophilized, for solutionIntravenous2 g
Prices
Unit descriptionCostUnit
Gemzar 1 gm Solution Vial903.93USD vial
Gemzar 1 gram vial869.16USD vial
Gemzar 200 mg Solution Vial180.78USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5464826No1995-11-072013-05-07US flag
US4808614No1989-02-282010-05-15US flag
US9241948No2016-01-262033-07-01US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)168.64 °CNot Available
water solubilitySolubleNot Available
logP-1.4Not Available
pKa3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility22.3 mg/mLALOGPS
logP0.14ALOGPS
logP-1.5ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)11.52ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area108.38 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity53.25 m3·mol-1ChemAxon
Polarizability21.45 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9814
Blood Brain Barrier+0.9693
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.8317
P-glycoprotein inhibitor INon-inhibitor0.9557
P-glycoprotein inhibitor IINon-inhibitor0.9106
Renal organic cation transporterNon-inhibitor0.939
CYP450 2C9 substrateNon-substrate0.8634
CYP450 2D6 substrateNon-substrate0.8484
CYP450 3A4 substrateNon-substrate0.6016
CYP450 1A2 substrateNon-inhibitor0.8958
CYP450 2C9 inhibitorNon-inhibitor0.8633
CYP450 2D6 inhibitorNon-inhibitor0.8787
CYP450 2C19 inhibitorNon-inhibitor0.8478
CYP450 3A4 inhibitorNon-inhibitor0.9032
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8862
Ames testNon AMES toxic0.6793
CarcinogenicityNon-carcinogens0.8286
BiodegradationNot ready biodegradable0.9948
Rat acute toxicity2.1220 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9948
hERG inhibition (predictor II)Non-inhibitor0.8314
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0930000000-e2122f1423d3060097b9
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0790000000-e66897c78fa010a45ab8
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0cfs-0910000000-e4e73c07b687772a1108
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-99f619802e3ba7bd8b2e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-18dd55d7372a11b9dfb7
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-1900000000-fdc016f6d17808e4cf1b
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-5900000000-ec478d4dfe03f80b91ad
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0790000000-0d953fc9632751f00f72
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-07xs-0920000000-0e8154089a57b6bef7c4
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-c54a530153a028d6ffcc
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-1f4cd6bc7d377fe7731e
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0900000000-c3cdcfa5d386ac7222fa
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0aor-4900000000-337f45a27b7b12b1b2f0
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-0920000000-52d24e07b71b7d08dcdb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0190000000-6d052797bc5b8b31bf7b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03dl-0900000000-01d92fca070f980c2668
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-95712722811cd50ab160
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0190000000-b97d64dba479bbac0253
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0930000000-fce77aa139fbedd4910b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-179a77c420afc3af2544
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-1900000000-5569d5d510ca5c1a84ef
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-2900000000-eb92e15ff6bb6fafe1dd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-5900000000-7cec5b636c875dcbfced
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0190000000-8d1e58453b0a991c8106
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0930000000-4739133fc80b45fc52ba
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-8fc0422b65b946f62385
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-1900000000-da3f8b2e4b3babb2a4f0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-2900000000-ea359abde4b5c6deb936
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-5900000000-f8e5e85ba0cd765dff4c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0900000000-18896272b82c17bec731

Targets

Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Cross-linking/alkylation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Hastak K, Alli E, Ford JM: Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin. Cancer Res. 2010 Oct 15;70(20):7970-80. doi: 10.1158/0008-5472.CAN-09-4521. Epub 2010 Aug 26. [PubMed:20798217]
  2. Ledermann JA, Gabra H, Jayson GC, Spanswick VJ, Rustin GJ, Jitlal M, James LE, Hartley JA: Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer. Clin Cancer Res. 2010 Oct 1;16(19):4899-905. doi: 10.1158/1078-0432.CCR-10-0832. Epub 2010 Aug 18. [PubMed:20719935]
  3. Garcia-Diaz M, Murray MS, Kunkel TA, Chou KM: Interaction between DNA Polymerase lambda and anticancer nucleoside analogs. J Biol Chem. 2010 May 28;285(22):16874-9. doi: 10.1074/jbc.M109.094391. Epub 2010 Mar 26. [PubMed:20348107]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
Specific Function
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name
RRM1
Uniprot ID
P23921
Uniprot Name
Ribonucleoside-diphosphate reductase large subunit
Molecular Weight
90069.375 Da
References
  1. Kwon WS, Rha SY, Choi YH, Lee JO, Park KH, Jung JJ, Kim TS, Jeung HC, Chung HC: Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenet Genomics. 2006 Jun;16(6):429-38. [PubMed:16708051]
  2. Rosell R, Cobo M, Isla D, Camps C, Massuti B: Pharmacogenomics and gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v13-16. [PubMed:16807441]
  3. Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, Simon G: RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006 Oct 10;24(29):4731-7. Epub 2006 Sep 11. [PubMed:16966686]
  4. Smid K, Bergman AM, Eijk PP, Veerman G, van Haperen VW, van den Ijssel P, Ylstra B, Peters GJ: Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1001-7. [PubMed:17065054]
  5. Nakahira S, Nakamori S, Tsujie M, Takahashi Y, Okami J, Yoshioka S, Yamasaki M, Marubashi S, Takemasa I, Miyamoto A, Takeda Y, Nagano H, Dono K, Umeshita K, Sakon M, Monden M: Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int J Cancer. 2007 Mar 15;120(6):1355-63. [PubMed:17131328]
  6. Cerqueira NM, Fernandes PA, Ramos MJ: Understanding ribonucleotide reductase inactivation by gemcitabine. Chemistry. 2007;13(30):8507-15. [PubMed:17636467]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Thymidylate synthase activity
Specific Function
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name
TYMS
Uniprot ID
P04818
Uniprot Name
Thymidylate synthase
Molecular Weight
35715.65 Da
References
  1. Rosell R, Taron M, Sanchez JM, Moran T, Reguart N, Besse B, Isla D, Massuti B, Alberola V, Sanchez JJ: The promise of pharmacogenomics: gemcitabine and pemetrexed. Oncology (Williston Park). 2004 Nov;18(13 Suppl 8):70-6. [PubMed:15655942]
  2. Huang CL, Yokomise H, Fukushima M, Kinoshita M: Tailor-made chemotherapy for non-small cell lung cancer patients. Future Oncol. 2006 Apr;2(2):289-99. [PubMed:16563096]
  3. Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, Danesi R: Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol. 2005 Jul;68(1):110-8. Epub 2005 Mar 28. [PubMed:15795320]
  4. Zhao XD, Zhang Y: [Routine chemotherapeutic drug treatment effectiveness predictive molecules and chemotherapeutic drug selection]. Ai Zheng. 2006 Dec;25(12):1577-80. [PubMed:17166391]
  5. Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Del Tacca M, Danesi R: Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol Cancer Ther. 2006 Jun;5(6):1387-95. [PubMed:16818496]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [PubMed:16818276]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Uridylate kinase activity
Specific Function
Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as...
Gene Name
CMPK1
Uniprot ID
P30085
Uniprot Name
UMP-CMP kinase
Molecular Weight
22222.175 Da
References
  1. Vernejoul F, Ghenassia L, Souque A, Lulka H, Drocourt D, Cordelier P, Pradayrol L, Pyronnet S, Buscail L, Tiraby G: Gene therapy based on gemcitabine chemosensitization suppresses pancreatic tumor growth. Mol Ther. 2006 Dec;14(6):758-67. Epub 2006 Sep 25. [PubMed:17000136]
  2. Hsu CH, Liou JY, Dutschman GE, Cheng YC: Phosphorylation of Cytidine, Deoxycytidine, and Their Analog Monophosphates by Human UMP/CMP Kinase Is Differentially Regulated by ATP and Magnesium. Mol Pharmacol. 2005 Mar;67(3):806-14. Epub 2004 Nov 18. [PubMed:15550676]
  3. Maring JG, Groen HJ, Wachters FM, Uges DR, de Vries EG: Genetic factors influencing pyrimidine-antagonist chemotherapy. Pharmacogenomics J. 2005;5(4):226-43. [PubMed:16041392]
  4. Lam W, Leung CH, Bussom S, Cheng YC: The impact of hypoxic treatment on the expression of phosphoglycerate kinase and the cytotoxicity of troxacitabine and gemcitabine. Mol Pharmacol. 2007 Sep;72(3):536-44. Epub 2007 Jun 12. [PubMed:17565005]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
Gene Name
CDA
Uniprot ID
P32320
Uniprot Name
Cytidine deaminase
Molecular Weight
16184.545 Da
References
  1. Giovannetti E, Laan AC, Vasile E, Tibaldi C, Nannizzi S, Ricciardi S, Falcone A, Danesi R, Peters GJ: Correlation between cytidine deaminase genotype and gemcitabine deamination in blood samples. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):720-5. doi: 10.1080/15257770802145447. [PubMed:18600531]
  2. Gusella M, Pasini F, Bolzonella C, Meneghetti S, Barile C, Bononi A, Toso S, Menon D, Crepaldi G, Modena Y, Stievano L, Padrini R: Equilibrative nucleoside transporter 1 genotype, cytidine deaminase activity and age predict gemcitabine plasma clearance in patients with solid tumours. Br J Clin Pharmacol. 2011 Mar;71(3):437-44. doi: 10.1111/j.1365-2125.2010.03838.x. [PubMed:21284703]
  3. Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [PubMed:19514966]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based...
Gene Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
Molecular Weight
30518.315 Da
References
  1. Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [PubMed:19514966]
  2. Marechal R, Mackey JR, Lai R, Demetter P, Peeters M, Polus M, Cass CE, Salmon I, Deviere J, Van Laethem JL: Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma. Cancer. 2010 Nov 15;116(22):5200-6. doi: 10.1002/cncr.25303. [PubMed:20669326]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Bergman AM, Pinedo HM, Talianidis I, Veerman G, Loves WJ, van der Wilt CL, Peters GJ: Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. Br J Cancer. 2003 Jun 16;88(12):1963-70. [PubMed:12799644]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name
ABCC10
Uniprot ID
Q5T3U5
Uniprot Name
Multidrug resistance-associated protein 7
Molecular Weight
161627.375 Da
References
  1. Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. doi: 10.1158/0008-5472.CAN-08-1420. [PubMed:19118001]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Santini D, Vincenzi B, Fratto ME, Perrone G, Lai R, Catalano V, Cass C, Ruffini PA, Spoto C, Muretto P, Rizzo S, Muda AO, Mackey JR, Russo A, Tonini G, Graziano F: Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer. J Cell Physiol. 2010 May;223(2):384-8. doi: 10.1002/jcp.22045. [PubMed:20082300]
  2. Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [PubMed:16818276]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine)....
Gene Name
SLC28A1
Uniprot ID
O00337
Uniprot Name
Sodium/nucleoside cotransporter 1
Molecular Weight
71583.18 Da
References
  1. Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [PubMed:10547395]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, ...
Gene Name
SLC29A2
Uniprot ID
Q14542
Uniprot Name
Equilibrative nucleoside transporter 2
Molecular Weight
50112.335 Da
References
  1. Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [PubMed:10547395]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function
Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtyp...
Gene Name
SLC28A3
Uniprot ID
Q9HAS3
Uniprot Name
Solute carrier family 28 member 3
Molecular Weight
76929.61 Da
References
  1. Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD: Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008. Epub 2009 Jan 22. [PubMed:19164483]

Drug created on June 13, 2005 07:24 / Updated on September 22, 2020 02:10

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